Pre-erythrocytic vaccine antigen (PEVA) candidates are transcribed during liver stage (LS) development. PEVA immunogens are recognized by CD8+ and CD4+ T cells in protected rodents and naturally exposed humans. The LMIV Pathogenesis and Immunity Section and SBRI have assessed the protective efficacy of some of these immunogens after DNA vaccination in rodent models of malaria. Our next objective is to establish the nonhuman primate and human models of protective pre-erythocytic immunity for further studies, to identify additional antigens that may be contributing to protective pre-erythrocytic immunity, and to assess the efficacy of leading immunogens in animals models that can guide the prioritization of those antigens to be tested in humans. During the past fiscal year, LMIV scientists have accomplished the following: 1. Initiated studies of nonhuman primate models of pre-erythrocytic malaria immunity, using whole organism and subunit vaccine strategies 2. Identified an additional panel of candidate pre-erythrocytic antigens that should be assessed in mluse models 3. Determined that naturally exposed African children develop CD8 T cell interferon gamma responses against leading PEVA antigens 4. Established an in vitro imaging system to visualize T cell killing of infected hepatocytes